Over the past 18 years we have conducted a series of multi-disciplinary studies of patients with chronic fatigue, later defined Chronic Fatigue Syndrome. These have included virologic, immunologic, neurologic, endocrinologic, psychologic, and therapeutic studies. Despite numerous studies, we still have no consistent laboratory abnormality that permits a clear diagnosis of the Chronic Fatigue Syndrome. We assisted the CDC and international groups in development and revision of case definitions by which the diagnosis is made through exclusion. Within the past few years our studies have concentrated in a few key areas. First, we have continued studies since our original findings in 1991 of alterations in the hypothalamic-pituitary-adrenal axis. We completed and will publish studies in which the axis was stimulated by arginine-vasopressin infusions to stimulate the axis. This year, we initiated a collaboration with investigators in NICHD to study responses of the axis to stimulation with interleukin-6. We completed a study of seasonality in CFS and another study of self-reported chemical sensitivities. We completed and reported this year a study of memory and central fatigue using cortical magnetic stimulation. This past year we completed a preliminary report of the results of a placebo-controlled trial of low-dose hydrocortisone. We found significant suppression of the adrenal gland and clinical improvement that was too modest to justify the risk of adrenal insufficiency. The work continues in this multi-disciplinary fashion.